Rozlytrek 200 mg hard capsules

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
• This leaflet has been written as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace ‘you’ with ‘your child’ throughout.

1. What Rozlytrek is and what it is used for
2. What you need to know before you take Rozlytrek
3. How to take Rozlytrek
4. Possible side effects
5. How to store Rozlytrek
6. Contents of the pack and other information

Rozlytrek is a cancer medicine that contains the active substance ‘entrectinib’.

Rozlytrek is used to treat either:

• adults and children 12 years of age and older with solid tumours (cancer) in various parts of the body that are caused by a change in a gene called ‘neurotrophic tyrosine receptor kinase (NTRK)’ or
• adults with a type of lung cancer called ‘non-small cell lung cancer’ (NSCLC) that is caused by a change in a gene called ‘ROS1’.

This medicine is used for solid tumour cancers when:

• a test has shown that your cancer cells have a change in genes called ‘NTRK’ (see ‘How Rozlytrek works’ below), and
• your cancer has spread within the affected organ or to other organs in your body or if surgery to remove the cancer is likely to cause severe complications, and
• you have not previously been given medicines called ‘NTRK inhibitors’
• other treatments have not worked or are not suitable for you.

This medicine is used if your lung cancer (NSCLC):

• is ‘ROS1-positive’ – this means that your cancer cells have a change in a gene called ‘ROS1’ (see ‘How Rozlytrek works’ below), and
• is advanced – for example, has spread to other parts of your body (metastatic), and
• you have not previously been given medicines called ‘ROS1 inhibitors’.

Rozlytrek works by blocking the action of faulty enzymes. These faulty enzymes are caused by a change in the NTRK or ROS1 genes that make them. The faulty enzymes make the cancer cells grow.

Rozlytrek may slow down or stop the growth of the cancer. It may also help to shrink your cancer.

• if you are allergic to entrectinib or any of the other ingredients of this medicine (listed in section 6).

If you are not sure, talk to your doctor, pharmacist or nurse before taking Rozlytrek.

Talk to your doctor, pharmacist or nurse before taking Rozlytrek if:

• you have recently had memory loss, confusion, hallucinations, or mental status changes
• you have had fractured bones, or conditions which may increase your risk of breaking bones, called ‘osteoporosis’ or ‘osteopaenia’
• you take medicine to lower the uric acid in your blood
• you have heart failure (when your heart struggles to pump blood to supply oxygen to the body) – signs can include cough, feeling short of breath, or swelling in your legs or arms
• you have ever had heart problems or a heart conduction problem called ‘prolonged QTc interval’ – this is shown on an ‘electro-cardiogram’ (ECG), or by low levels of electrolytes in your blood
• you have an inherited problem called ‘galactose intolerance’, ‘congenital lactase deficiency’ or ‘glucose-galactose malabsorption’.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking Rozlytrek.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Rozlytrek can affect the way some other medicines work. Also, some other medicines can affect the way Rozlytrek works.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines for:

• fungal infections (anti-fungals) – such as ketoconazole, itraconazole, voriconazole, or posaconazole
• AIDS/HIV infection – such as ritonavir or saquinavir
• depression – such as paroxetine, fluvoxamine, or a herbal medicine for depression - St. John’s Wort
• stopping seizures or fits – such as phenytoin, carbamazepine, or phenobarbital
• tuberculosis – such as rifampicin, or rifabutin
• solid cancers and blood cancer – topotecan, lapatinib, mitoxantrone, apalutamide, or methotrexate
• inflammed joints or joint autoimmune disease (rheumatoid arthritis) – methotrexate
• migraines – ergotamine
• severe pain – fentanyl
• mental illness (psychoses) or Tourette Syndrome – pimozide
• irregular heart rate – quinidine
• stopping the formation of blood clots – warfarin or dabigatran etexilate
• gastric reflux (heartburn) – cisapride or omeprazole
• lowering blood cholesterol – atorvastatin, pravastatin, or rosuvastatin
• suppressing your body’s immune system, or stopping your body from rejecting an organ transplant – sirolimus, tacrolimus, or cyclosporin
• lowering blood sugar levels – repaglinide or tolbutamide
• high blood pressure – bosentan, felodipine, nifedipine, or verapamil
• inflammation or nausea – dexamethasone

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Rozlytrek.

Do not drink grapefruit juice or eat grapefruit or Seville oranges during your treatment with this medicine. It may increase the amount of the medicine in your blood to a harmful level.

You must avoid becoming pregnant while taking this medicine because it could harm the baby. If you are able to become pregnant, you must use highly effective contraception:

• while on treatment, and
• for at least 5 weeks after stopping treatment.

It is not known if Rozlytrek can reduce the effect of birth control medicines (contraceptive pills or implanted hormonal contraceptives). You should use another reliable method of birth control such as a barrier method (such as a condom).

Talk to your doctor about the right methods of contraception for you and your partner.

Your female partner must avoid becoming pregnant while you are taking this medicine because it could harm the baby. If your female partner is able to become pregnant, you must use highly effective contraception:

• while on treatment, and
• for at least 3 months after stopping treatment.

Talk to your doctor about the right methods of contraception for you and your partner.

• Do not take Rozlytrek if you are pregnant. This is because it may harm your baby.
• If you become pregnant when taking the medicine or during the 5 weeks after taking your last dose, tell your doctor straight away.

Do not breast-feed while taking this medicine. This is because it is not known if Rozlytrek can pass over into breast milk and could therefore harm your baby.

Rozlytrek may affect your ability to drive, ride a bicycle, or use machines. Rozlytrek may cause you to:

• have blurred vision
• feel tired, dizzy, or pass out
• have changes in your mental status, feel confused or see things that are not there (hallucinations).

If this happens, you should not drive, ride a bicycle, or operate heavy machines until you feel better. Talk to your doctor or pharmacist about whether it is okay for you to drive, ride a bicycle, or use machines.

• lactose - a type of sugar. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
• sunset yellow FCF (E110) in 200 mg hard capsules only. This is a colouring agent, which may cause allergic reactions.

For adults

• The recommended dose is 3 capsules of 200 mg once a day (total amount 600 mg).
• If you feel unwell, your doctor may lower your dose, stop treatment for a short time or stop treatment completely.

For children

• Rozlytrek can be used in children 12 years of age and older.
• Your child’s doctor will work out the correct dose to use – based on the height and weight of the child.
• Your child’s doctor will review the dose and change it as needed.

Rozlytrek can be taken with or without food. Swallow each capsule whole. Do not open or dissolve the capsules since the contents of the capsule are very bitter.

If you vomit immediately after taking a dose of Rozlytrek, take another dose.

If you take more Rozlytrek than you should, talk to a doctor or go to hospital straight away. Take the medicine pack and this leaflet with you.

• If your next dose is more than 12 hours later, take the missed dose as soon as you remember.
• If there are less than 12 hours until your next dose, do not take the missed dose. Take your next dose at the usual time.
• Do not take a double dose to make up for a missed dose.

Do not stop taking this medicine without talking to your doctor first. It is important to take this medicine every day for as long as your doctor prescribes it for you.

Tell your doctor straight away if you notice any of the following serious side effects. Your doctor may lower your dose, stop your treatment for a short time or stop your treatment completely if:

• you have cough, feel short of breath, or swelling in your legs or arms (fluid retention) – these can be signs of heart problems (congestive heart failure)
• you feel confused, have mood changes, memory problems or see things that are not there (hallucinations)
• you feel dizzy or light-headed, or feel your heart beating irregularly or fast – this may be a sign of an abnormal heartbeat
• you notice any joint pain, bone pain, deformities or changes in your ability to move, as this may be a sign of fractures
• you have kidney problems or arthritis – you may have high uric acid levels in your blood

Tell your doctor straight away if you notice any of the side effects above.

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Very common: may affect more than 1 in 10 people:

• feeling tired
• changes in taste
• feeling unsteady or dizzy
• blurred vision
• swelling
• diarrhoea or constipation
• being or feeling sick
• difficulty swallowing
• abnormal sense of touch which feels like itching, tingling or burning sensation
• rash
• feeling short of breath
• cough or fever
• headache
• weight gain
• vomiting
• muscle pain or weakness
• pain including back pain, neck pain, musculoskeletal pain, pain in limbs
• stomach pain
• joint pain
• abnormal unpleasant sensation in your arms or legs
• loss of muscle coordination, being unsteady when walking
• disturbance in normal sleep patterns
• lung infection
• urinary tract infection
• cannot empty your bladder completely
• loss of appetite
• low blood pressure
• decreased number of a type of white blood cell called neutrophils
• lack of enough red blood cells (anaemia)
• increased blood levels of certain liver enzymes (AST/ALT)
• increased blood level of creatinine (something normally removed by the kidneys into the urine)

Common: may affect up to 1 in 10 people:

• mood disorders
• dehydration
• fluid around your lungs
• fainting
• skin being more sensitive to sunlight

Uncommon: may affect less than 1 in 100 people:

• changes in certain chemicals in your blood caused by fast breakdown of tumour cells – this may cause damage to organs, including the kidneys, heart, and liver.
• Inflammation of the heart muscle

Tell your doctor, pharmacist or nurse if you notice any of the side effects above.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is entrectinib.

Rozlytrek 100 mg: each capsule contains 100 mg entrectinib

Rozlytrek 200 mg: each capsule contains 200 mg entrectinib

The other ingredients are:

• Capsule content: tartaric acid (E334), lactose (see section 2 ‘Rozlytrek contains lactose’), hypromellose (E464), crospovidone (E1202), microcrystalline cellulose (E460), silica, colloidal anhydrous (E551), magnesium stearate (E470b).
• Capsule shell: hypromellose (E464), titanium dioxide (E171), yellow iron oxide (E172; for Rozlytrek 100 mg capsule), sunset yellow FCF (E110; for Rozlytrek 200 mg capsule). See section 2 ‘Rozlytrek contains sunset yellow FCF (E110)’.
• Printing ink: shellac, propylene glycol, indigo carmine aluminium lake (E132).

Rozlytrek 100 mg hard capsules are opaque yellow with ENT 100 imprinted in blue on the body.

Rozlytrek 200 mg hard capsules are opaque orange with ENT 200 imprinted in blue on the body.

The capsules are provided in bottles containing either:

• 30 hard capsules of Rozlytrek 100 mg, or
• 90 hard capsules of Rozlytrek 200 mg.